Legal framework

The regulatory framework for advanced therapy medicinal products (ATMPs) is designed to ensure the free movement of these medicines within the European Union (EU), to facilitate their access to the EU market, and to foster the competitiveness of European pharmaceutical companies in the field, while guaranteeing the highest level of health protection for patients.

The Regulation established the Committee for Advanced Therapies (CAT) as a multidisciplinary committee, whose primary responsibility is to assess the quality, safety and efficacy of ATMPs, and to follow scientific developments in the field. As of June 2009, the CAT issues scientific recommendations on ATMPs classification.

ATMP classification

The CAT issues scientific recommendation on ATMPs classification in accordance with Article 17 of the ATMP Regulation. Its recommendations are based on definitions laid down in EU legislative texts:

Part IV of Annex I to Directive 2001/83/EC provides the definitions for 'gene-therapy medicinal product' and 'somatic cell-therapy medicinal product'.

Certification of quality and non-clinical data for micro-, small- and medium-sized enterprises (SMEs)

This procedure was introduced in accordance with Article 18 of the ATMP Regulation and in accordance with Commission Regulation (EC) No 668/2009 implementing Regulation (EC) No 1394/2007 with regard to the evaluation and certification of quality and non-clinical data relating to ATMPs developed by SMEs.

EU legislative framework applicable to ATMPs

Directive 2001/83/EC (consolidated version 16/11/2012) of November 2001 relating to medicinal products for human use;

Regulation (EC) No 726/2004 (consolidated version 5/6/2013) of March 2004 on procedures for the authorisation and supervision of medicines for human and veterinary use and establishing the European Medicines Agency.

In addition, Commission Directive 2009/120/EC (amending Directive 2001/83/EC) updated the definitions and detailed scientific and technical requirements for gene-therapy medicinal products and somatic cell-therapy medicinal products. It also established detailed scientific and technical requirements for tissue-engineered products, as well as for ATMPs containing devices and combined ATMPs.

Clinical Trials Directive and Clinical Trials Regulation

Companies developing ATMPs must ensure that the standards of good clinical practice (GCP) are applied when carrying out clinical trial studies:

Directive 2001/20/EC of April 2001 lays down approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicines for human use.

In April 2014 the new Regulation EU No 536/2014 on clinical trials on medicinal products for human use, repealing Directive 2001/20/EC, was adopted. The Regulation entered into force on 16 June 2014 but will apply no earlier than 28 May 2016.

Good clinical practice and good manufacturing practice

Companies developing ATMPs must be aware of legislation applicable to different stages of the process, including requirements on GCP and good manufacturing practice (GMP):

Commission Directive 2005/28/EC of April 2005 laying down principles and detailed guidelines for GCP as regards investigational medicines for human use, as well as the requirements for authorisation of the manufacturing or importation of such products.

Commission Directive 2003/94/EC of October 2003 laying down the principles and guidelines of GMP in respect of medicines for human use and investigational medicines for human use.

Paediatric Regulation

Provisions of the Paediatric Regulation are applicable for ATMPs including the obligation to include the results of studies as described in an agreed paediatric investigation plan, unless the medicine is exempt because of a deferral or waiver.

Variations Regulation

Commission Regulation (EC) No 1234/2008 of November 2008 (the Variations Regulation) lays down provisions concerning the examination of variations to the terms of all marketing authorisations for human and veterinary medicines.

Pharmacovigilance legislation

A package of legislation, first adopted in 2010 and further supplemented in 2012, lays down provisions to reinforce pharmacovigilance in the EU. This framework is applicable to all medicines, including ATMPs:

Personal data protection

Directive 95/46/EC is the reference text, at European level, on the protection of personal data. It sets up a regulatory framework which seeks to strike a balance between a high level of protection for the privacy of individuals and the free movement of personal data within the EU.

Tissues and Cells Directive and Traceability

If tissues and cells are being used as starting materials in a medicinal product, applicants should consult:

Directive 2004/23/EC, also known as the European Tissues and Cells Directive, covering standards for donation, procurement and testing, processing, preservation, storage and distribution of human tissues and cells, as well as its technical implementing directives:

Directive 2006/17/EC, the First Technical Directive, covering certain technical requirements for the donation, procurement and testing of human tissues and cells;

Directive 2006/86/EC, the Second Technical Directive, covering standards for traceability, notification of serious adverse reactions and events, and requirements for coding processing, preservation, storage and distribution of human tissues and cells;

Directive 2015/566, as regards the procedures for verifying the equivalent standards of quality and safety of imported tissues and cells.

Other relevant EU legislation

The following legislation may also apply to ATMPs if the listed categories are relevant to the ATMP concerned.

Human blood and blood components

Directive 2002/98/EC (amending Directive 2001/83/EC) of January 2003 sets standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components.

Genetically modified organisms

If an ATMP contains genetically modified organisms, companies must follow relevant legislation on the deliberate release of genetically modified organisms into the environment:

Directive 2001/18/EC (repealing Council Directive 90/220/EEC) of March 2001 put in place a step-by-step process to assess possible environmetnal and health risks.

Conditional marketing authorisation

For certain categories of medicinal products, in order to meet unmet medical needs of patients and in the interest of public health, it may be necessary to grant marketing authorisations on the basis of less complete data than is normally required. In such cases, the granting of a conditional marketing authorisation may be recommended subject to certain specific obligations to be reviewed annually. This may apply to medicinal products for human use that fall under Article 3(1) and (2) of Regulation (EC) No 726/2004.